Summary: Longer duration of estrogen exposure hormone therapy was associated with better cognition in older adult women.
Estrogen has a significant role in overall brain health and cognitive function. That’s why so many studies focused on the prevention of cognitive decline consider the effect of reduced estrogen levels during the menopause transition. A new study suggests a cognitive benefit from a longer reproductive window complemented with hormone therapy. Study results are published online today in Menopause.
Because women comprise two-thirds of the 5.5 million cases of Alzheimer’s disease in the United States, researchers have long suspected that sex-specific factors such as estrogen may contribute to women’s increased risk for the disease. Multiple studies have previously suggested a role for estrogen in promoting memory and learning.
In this newest study involving more than 2,000 postmenopausal women, researchers followed participants over a 12-year period to examine the association between estrogen and cognitive decline. More specifically, they focused on the duration of a woman’s exposure to estrogen, taking into account such factors as time of menarche to menopause, number of pregnancies, duration of breastfeeding, and use of hormone therapy.
The researchers concluded that a longer duration of estrogen exposure is associated with better cognitive status in older adult women. Furthermore, they documented that these beneficial effects are extended with the use of hormone therapy, especially in the oldest women in the sample. Women who initiated hormone therapy earlier showed higher cognitive test scores than those who started taking hormones later, providing some support for the critical window hypothesis of hormone therapy.
Study results appear in the article “Lifetime estrogen exposure and cognition in late life: The Cache County Study.”
“Although the assessment of the risk-to-benefit balance of hormone therapy use is complicated and must be individualized, this study provides additional evidence for beneficial cognitive effects of hormone therapy, particularly when initiated early after menopause. This study also underscores the potential adverse effects of early estrogen deprivation on cognitive health in the setting of premature or early menopause without adequate estrogen replacement,” says Dr. Stephanie Faubion, NAMS medical director.
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Lifetime estrogen exposure and cognition in late life: The Cache County Study
Objective: Prevalence of Alzheimer’s disease (AD) is higher for women, possibly influenced by sex-dependent effects of the estrogen. We examined the association between estrogen and cognitive decline in over 2,000 older adult women in a 12-year population-based study in Cache County, Utah.
Methods: The baseline sample included 2,114 women (mean age = 74.94 y, SD = 6.71) who were dementia-free at baseline and completed a women’s health questionnaire, asking questions regarding reproductive history and hormone therapy (HT). Endogenous estrogen exposure (EEE) was calculated taking the reproductive window (age at menarche to age at menopause), adjusted for pregnancy and breastfeeding. HT variables included duration of use, HT type (unopposed; opposed), and time of HT initiation. A modified version of the Mini-Mental State Examination (3MS) was administered at four triennial waves to assess cognitive status. Linear mixed-effects models examined the relationship between estrogen exposure and 3MS score over time.
Results: EEE was positively associated with cognitive status (β = 0.03, P = 0.054). In addition, longer duration of HT use was positively associated with cognitive status (β = 0.02, P = 0.046) and interacted with age; older women had greater benefit compared with younger women. The timing of HT initiation was significantly associated with 3MS (β = 0.55, P = 0.048), with higher scores for women who initiated HT within 5 years of menopause compared with those initiating HT 6-or-more years later.
Conclusions: Our results suggest that longer EEE and HT use, especially in older women, are associated with higher cognitive status in late life.
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